Effectiveness of a normative nutrition intervention (diet, physical activity and breastfeeding) on maternal nutrition and offspring growth: the Chilean maternal and infant nutrition cohort study (CHiMINCs).

BACKGROUND: Maternal obesity before and during pregnancy predicts maternal and infant risks of obesity and its associated metabolic conditions. Dietary and physical activity recommendations during pregnancy as well as weight monitoring are currently available in the Chilean primary health care system. However some of these recommendations are not updated and most of them are poorly implemented. We seek to assess the effectiveness of an intervention that enhances the implementation of updated nutrition health care standards (diet, physical activity, and breastfeeding promotion) during pregnancy on maternal weight gain and infant growth. METHODS: DESIGN & SETTING: Cluster randomized controlled trial. The cluster units will be 12 primary health care centers from two counties (La Florida and Puente Alto) from the South-East Area of Santiago randomly allocated to: 1) enhanced nutrition health care standards (intervention group) or 2) routine care (control group). PARTICIPANTS: Women seeking prenatal care before 15 weeks of gestation, residing within a catchment area of selected health centers, and who express that they are not planning to change residence will be invited to participate in the study. Pregnant women classified as high risk according to the Chilean norms (i.e age 40 years, multiple gestation, pre-gestational medical conditions, previous pregnancy-related issues) and/or underweight will be excluded. INTERVENTION: Pregnant women who attend intervened health care centers starting at their first prenatal visit will receive advice regarding optimal weight gain during pregnancy and diet and physical activity counseling-support. Pregnant women who attend control health clinics will receive routine antenatal care according to national guidelines. We plan to recruit 200 women in each health center. Assuming a 20% loss to follow up, we expect to include 960 women per arm. MAIN OUTCOME MEASURES: 1) Achievement of adequate weight gain based on IOM 2009 recommendations and adequate glycaemic control at 24-28 weeks of pregnancy according to ADA 2011, and 2) healthy infant growth during the first year of age based on WHO standards. DISCUSSION: We expect that the intervention will benefit the participants in achieving adequate weight gain & metabolic control during pregnancy as well as adequate infant growth as a result of an increased impact of standard nutrition and health care practices. Gathered information should contribute to a better understanding of how to develop effective interventions to halt the maternal obesity epidemic and its associated co-morbidities in the Chilean population. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT01916603

Latin America and the Caribbean code against cancer: Developing evidence-based recommendations to reduce the risk of cancer in Latin America and the Caribbean

Latin America and the Caribbean (LAC) has a population of more than 650 million inhabitants (8.5% of the world population),1 with a cancer incidence of more than 1.4 million new patients and more than 670,000 deaths in 2018. These figures will increase by 78% by 2040 to more than 2.5 million people diagnosed with cancer each year, and these patients will require medical attention, care, and support. However, many of these new cancer diagnoses can be prevented through public policies, supportive environments, and lifestyles that promote health and prevent cancer (Fig 1).2 In the LAC region, there are many organizations and institutions providing information on cancer prevention, including national cancer institutes, cancer societies and foundations, and public health agencies. Nevertheless, the information is frequently confusing, overwhelming, or even contradictory. The scientific source and credibility, as well as the primary message, differ according to the type of organization that provides the information (eg, patient organization, scientific or governmental institution).For the LAC region, a coalition of institutions and international organizations has joined forces to adapt the European Code to the cancer risks and situation in the LAC region. This involves collecting, analyzing, and evaluating the scientific evidence to support suitable cancer prevention recommendations to the LAC context. A multistakeholder participation in the project is a key approach to ensure that all players will be owners of the Code and true promoters. The coalition is composed of the Pan-American Health Organization (PAHO; also part of the WHO) and the IARC as leading international organizations; a Scientific Committee of senior researchers and distinguished leaders in cancer prevention from LAC; and an Advocacy Group representing important organizations in LAC, including the Latin American and Caribbean Society of Medical Oncology, the Network of Latin-American Cancer Institutes, the Healthy Caribbean Coalition, and the Association of Latin American Leagues Against Cancer.Fil: Cazap, Eduardo. Sociedad Latinoamericana y del Caribe de Oncología Médica; ArgentinaFil: de Almeida, Liz Maria. Instituto Nacional de Câncer Brasil Jose Alencar Gomes da Silva; BrasilFil: Arrossi, Silvina. Centro de Estudios de Estado y Sociedad; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: García, Patricia J.. Universidad Cayetano Heredia; PerúFil: Garmendia, María Luisa. Universidad de Chile; ChileFil: Gil, Enrique. South America Pan-American Health Organization; PerúFil: Hassel, Trevor. Healthy Caribbean Coalition; BarbadosFil: Mayorga, Rubén. South America Pan-American Health Organization; PerúFil: Mohar, Alejandro. Universidad Nacional Autónoma de México; MéxicoFil: Murillo, Raúl. Centro Javeriano de Oncología; ColombiaFil: Owen, Gabriel O.. Healthy Caribbean Coalition; BarbadosFil: Paonessa, Diego. Liga Argentina de Lucha contra el Cancer; ArgentinaFil: Santamaría, Julio. Centro Hemato Oncológico Panamá; PanamáFil: Tortolero Luna, Guillermo. Universidad de Puerto Rico; Puerto RicoFil: Zoss, Walter. Red de Institutos e Instituciones Nacionales de Cancer; BrasilFil: Herrero, Rolando. Agencia Internacional para la Investigación del Cáncer; FranciaFil: Luciani, Silvana. Pan-American Health Organization; Estados UnidosFil: Schüz, Joachim. Agencia Internacional para la Investigación del Cáncer; FranciaFil: Espina, Carolina. Agencia Internacional para la Investigación del Cáncer; Franci

International Consortium on Mammographic Density:methodology and population diversity captured across 22 countries

Mammographic density (MD) is a quantitative trait, measurable in all women, and is among the strongest markers of breast cancer risk. The population-based epidemiology of MD has revealed genetic, lifestyle and societal/environmental determinants, but studies have largely been conducted in women with similar westernized lifestyles living in countries with high breast cancer incidence rates. To benefit from the heterogeneity in risk factors and their combinations worldwide, we created an International Consortium on Mammographic Density (ICMD) to pool individual-level epidemiological and MD data from general population studies worldwide. ICMD aims to characterize determinants of MD more precisely, and to evaluate whether they are consistent across populations worldwide. We included 11755 women, from 27 studies in 22 countries, on whom individual-level risk factor data were pooled and original mammographic images were re-read for ICMD to obtain standardized comparable MD data. In the present article, we present (i) the rationale for this consortium; (ii) characteristics of the studies and women included; and (iii) study methodology to obtain comparable MD data from original re-read films. We also highlight the risk factor heterogeneity captured by such an effort and, thus, the unique insight the pooled study promises to offer through wider exposure ranges, different confounding structures and enhanced power for sub-group analyses

Effects of intubation timing in patients with COVID-19 throughout the four waves of the pandemic : a matched analysis

The primary aim of our study was to investigate the association between intubation timing and hospital mortality in critically ill patients with COVID-19-associated respiratory failure. We also analysed both the impact of such timing throughout the first four pandemic waves and the influence of prior non-invasive respiratory support on outcomes. This is a secondary analysis of a multicentre, observational and prospective cohort study that included all consecutive patients undergoing invasive mechanical ventilation due to COVID-19 from across 58 Spanish intensive care units (ICU) participating in the CIBERESUCICOVID project. The study period was between 29 February 2020 and 31 August 2021. Early intubation was defined as that occurring within the first 24 h of intensive care unit (ICU) admission. Propensity score (PS) matching was used to achieve balance across baseline variables between the early intubation cohort and those patients who were intubated after the first 24 h of ICU admission. Differences in outcomes between early and delayed intubation were also assessed. We performed sensitivity analyses to consider a different timepoint (48 h from ICU admission) for early and delayed intubation. Of the 2725 patients who received invasive mechanical ventilation, a total of 614 matched patients were included in the analysis (307 for each group). In the unmatched population, there were no differences in mortality between the early and delayed groups. After PS matching, patients with delayed intubation presented higher hospital mortality (27.3% versus 37.1%, p =0.01), ICU mortality (25.7% versus 36.1%, p=0.007) and 90-day mortality (30.9% versus 40.2%, p=0.02) when compared to the early intubation group. Very similar findings were observed when we used a 48-hour timepoint for early or delayed intubation. The use of early intubation decreased after the first wave of the pandemic (72%, 49%, 46% and 45% in the first, second, third and fourth wave, respectively; first versus second, third and fourth waves p<0.001). In both the main and sensitivity analyses, hospital mortality was lower in patients receiving high-flow nasal cannula (n=294) who were intubated earlier. The subgroup of patients undergoing NIV (n=214) before intubation showed higher mortality when delayed intubation was set as that occurring after 48 h from ICU admission, but not when after 24 h. In patients with COVID-19 requiring invasive mechanical ventilation, delayed intubation was associated with a higher risk of hospital mortality. The use of early intubation significantly decreased throughout the course of the pandemic. Benefits of such an approach occurred more notably in patients who had received high-flow nasal cannul

Clustering COVID-19 ARDS patients through the first days of ICU admission. An analysis of the CIBERESUCICOVID Cohort

Background Acute respiratory distress syndrome (ARDS) can be classified into sub-phenotypes according to different inflammatory/clinical status. Prognostic enrichment was achieved by grouping patients into hypoinflammatory or hyperinflammatory sub-phenotypes, even though the time of analysis may change the classification according to treatment response or disease evolution. We aimed to evaluate when patients can be clustered in more than 1 group, and how they may change the clustering of patients using data of baseline or day 3, and the prognosis of patients according to their evolution by changing or not the cluster.Methods Multicenter, observational prospective, and retrospective study of patients admitted due to ARDS related to COVID-19 infection in Spain. Patients were grouped according to a clustering mixed-type data algorithm (k-prototypes) using continuous and categorical readily available variables at baseline and day 3.Results Of 6205 patients, 3743 (60%) were included in the study. According to silhouette analysis, patients were grouped in two clusters. At baseline, 1402 (37%) patients were included in cluster 1 and 2341(63%) in cluster 2. On day 3, 1557(42%) patients were included in cluster 1 and 2086 (57%) in cluster 2. The patients included in cluster 2 were older and more frequently hypertensive and had a higher prevalence of shock, organ dysfunction, inflammatory biomarkers, and worst respiratory indexes at both time points. The 90-day mortality was higher in cluster 2 at both clustering processes (43.8% [n = 1025] versus 27.3% [n = 383] at baseline, and 49% [n = 1023] versus 20.6% [n = 321] on day 3). Four hundred and fifty-eight (33%) patients clustered in the first group were clustered in the second group on day 3. In contrast, 638 (27%) patients clustered in the second group were clustered in the first group on day 3.Conclusions During the first days, patients can be clustered into two groups and the process of clustering patients may change as they continue to evolve. This means that despite a vast majority of patients remaining in the same cluster, a minority reaching 33% of patients analyzed may be re-categorized into different clusters based on their progress. Such changes can significantly impact their prognosis

Mammographic density and ageing:A collaborative pooled analysis of cross-sectional data from 22 countries worldwide

BACKGROUND: Mammographic density (MD) is one of the strongest breast cancer risk factors. Its age-related characteristics have been studied in women in western countries, but whether these associations apply to women worldwide is not known. METHODS AND FINDINGS: We examined cross-sectional differences in MD by age and menopausal status in over 11,000 breast-cancer-free women aged 35-85 years, from 40 ethnicity- and location-specific population groups across 22 countries in the International Consortium on Mammographic Density (ICMD). MD was read centrally using a quantitative method (Cumulus) and its square-root metrics were analysed using meta-analysis of group-level estimates and linear regression models of pooled data, adjusted for body mass index, reproductive factors, mammogram view, image type, and reader. In all, 4,534 women were premenopausal, and 6,481 postmenopausal, at the time of mammography. A large age-adjusted difference in percent MD (PD) between post- and premenopausal women was apparent (-0.46 cm [95% CI: -0.53, -0.39]) and appeared greater in women with lower breast cancer risk profiles; variation across population groups due to heterogeneity (I2) was 16.5%. Among premenopausal women, the √PD difference per 10-year increase in age was -0.24 cm (95% CI: -0.34, -0.14; I2 = 30%), reflecting a compositional change (lower dense area and higher non-dense area, with no difference in breast area). In postmenopausal women, the corresponding difference in √PD (-0.38 cm [95% CI: -0.44, -0.33]; I2 = 30%) was additionally driven by increasing breast area. The study is limited by different mammography systems and its cross-sectional rather than longitudinal nature. CONCLUSIONS: Declines in MD with increasing age are present premenopausally, continue postmenopausally, and are most pronounced over the menopausal transition. These effects were highly consistent across diverse groups of women worldwide, suggesting that they result from an intrinsic biological, likely hormonal, mechanism common to women. If cumulative breast density is a key determinant of breast cancer risk, younger ages may be the more critical periods for lifestyle modifications aimed at breast density and breast cancer risk reduction

The evolution of the ventilatory ratio is a prognostic factor in mechanically ventilated COVID-19 ARDS patients

Background: Mortality due to COVID-19 is high, especially in patients requiring mechanical ventilation. The purpose of the study is to investigate associations between mortality and variables measured during the first three days of mechanical ventilation in patients with COVID-19 intubated at ICU admission. Methods: Multicenter, observational, cohort study includes consecutive patients with COVID-19 admitted to 44 Spanish ICUs between February 25 and July 31, 2020, who required intubation at ICU admission and mechanical ventilation for more than three days. We collected demographic and clinical data prior to admission; information about clinical evolution at days 1 and 3 of mechanical ventilation; and outcomes. Results: Of the 2,095 patients with COVID-19 admitted to the ICU, 1,118 (53.3%) were intubated at day 1 and remained under mechanical ventilation at day three. From days 1 to 3, PaO2/FiO2 increased from 115.6 [80.0-171.2] to 180.0 [135.4-227.9] mmHg and the ventilatory ratio from 1.73 [1.33-2.25] to 1.96 [1.61-2.40]. In-hospital mortality was 38.7%. A higher increase between ICU admission and day 3 in the ventilatory ratio (OR 1.04 [CI 1.01-1.07], p = 0.030) and creatinine levels (OR 1.05 [CI 1.01-1.09], p = 0.005) and a lower increase in platelet counts (OR 0.96 [CI 0.93-1.00], p = 0.037) were independently associated with a higher risk of death. No association between mortality and the PaO2/FiO2 variation was observed (OR 0.99 [CI 0.95 to 1.02], p = 0.47). Conclusions: Higher ventilatory ratio and its increase at day 3 is associated with mortality in patients with COVID-19 receiving mechanical ventilation at ICU admission. No association was found in the PaO2/FiO2 variation

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

Hypertension and the risk of breast cancer in chilean women: A case-control study

Background: Breast cancer is the most common cancer in women worldwide. Although different metabolic factors have been implicated in breast cancer development, the relationship between hypertension and breast cancer has not been elucidated. Aim: To evaluate hypertension as a risk factor for breast cancer in Chilean women of low and middle socio-economic status. Methods: We conducted an age-matched (1:1) case-control study in 3 hospitals in Santiago, Chile. Breast cancer cases (n=170) were histopathologically confirmed. Controls had been classified as Breast Imaging Reporting and Data System I (negative) or II (benign findings) within 6 months of recruitment. Blood pressure was measured using a mercury sphygmomanometer and standardized procedures. We used 2 hypertension cut-off points: blood pressures of ≥140/90 mmHg and ≥130/85 mmHg. Fasting insulin and glucose levels were assessed, and anthropometric, sociodemographic, and behavioral information were collected. Odds ratios and 95% co

Adherence to a physical activity intervention among older adults in a post-transitional middle income country: A quantitative and qualitative analysis

Objectives: The effectiveness of community level interventions depends to a great extent on adherence. Currently, information on factors related to adherence in older adults from developing countries is scarce. Our aim was to identify factors associated to adherence to a physical activity intervention in older adults from a post-transitional middle income country. Design, setting and participants: Using a combination of quantitative and qualitative methods we studied 996 older Chilean subjects (65-67.9 years at baseline) with low to medium socioeconomic status from 10 health centers randomized to receive a physical activity intervention as part of the CENEX cluster trial (ISRCTN48153354). Measurements: Using a multilevel regression model, the relationship between adherence (defined a priori as attendance at a minimum of 24 physical activity classes spread over at least 12 months) and individual, intervention-related and contextual factors was evaluated. We also conducted 40 semi-structured interviews with older adults (n=36) and instructors (n=4). Transcripts of the interviews were analyzed using content analysis to identify barriers and facilitators to adherence. Results Adherence to physical activity intervention was 42.6% (CI 95% 39.5 to 45.6). Depression, diabetes mellitus, percentage of impoverished households and rate of arrests for violent crimes in the neighborhood predicted less adherence (p<0.05) while being retired, participation in physical activity prior to the intervention, and green areas per habitant were positively associated with adherence (p<0.05). The qualitative interviews identified three primary barriers to adherence: current health problems, lack of time due to commitments for caring for family members, and being employed, and two primary facilitators to adherence: the health benefits attributed to the intervention and the opportunity the classes provided for social interaction with others: Conclusion: In order to enhance effectiveness of community exercise interventions, strategies to improve participation should be targeted to older adults from deprived areas and those with psychological and medical conditions. © 2012 Serdi and Springer-Verlag France